The Effect And Underlying Mechanism Of Trimetazidine Preconditioning And Ischemic Postconditioning On Ischemia-reperfusion Injury

Objective: To investigate and preliminarily explore the protective effects and underlying mechanism of trimetazidine and ischemia postconditioning on rat cardiac ischemia-reperfusion injury.Methods: We randomly divided 60 adult SD male rats into five groups(n=12):sham operation group(Sham group),ischemia-reperfusion group(IR group),ischemia postconditioning group(IP group),preconditioning by trimetazidine group(TMZ group),and ischemia postconditioning + trimetazidine group(IP+TMZ group),the suture in the sham operation group didn’t ligature the left anterior descending coronary artery(left anterior descending coronary artery,LAD),the other four groups ligature the LAD to established the cardiac ischemia-reperfusion models.In this experimental model,rats were subjected to ischemia for 30 minutes and then reperfused for 120 minutes,the ventricular arrhythmia of each group was observed and recorded and calculated.After reperfused,Take 2ml of the arterial blood from the abdominal and put it in a PE tube,and let it stand at room temperature for about 0.5-1 hour.Finally,centrifuge and select the supernatant.,Store in-80℃ultra-low temperature refrigerator.Using the xanthine oxidase method to measured SOD、MDA,and enzyme-linked immunoassay to measured Tn TI、IL-6、TNF-α、CKMB.After execution the rats,we quickly dissected the heart,and then rinsed the heart with ice salt water.Four rats in each group were fixed with 10%paraformaldehyde and embedded in paraffin.Application of TUNEL to detect cardiomyocyte apoptosis,and then calculate the apoptotic index and use hematoxylin-eosin staining to observe the microstructure of myocardial tissue.The other 4 rats were used for western blot to detect the expression of caspase3,caspase9,bax,bcl-2,and c-myc.Results: ⑴ Compared with Sham group: the arrhythmia scores of the other four groups increased,myocardial infarction area increased,SOD concentration decreased,CKMB concentration increased,MDA concentration increased,IL-6,TNF-αconcentration increased,apoptosis index increased,caspase3,Caspase9,bax increased,bcl-2,c-myc decreased.⑵Compared with IR group: IP group,TMZ group,IP+TMZ group arrhythmia score decreased,myocardial infarction area decreased,SOD concentration increased,CKMB concentration decreased,MDA concentration decreased,IL-6,TNF-α concentration decreased,cell apoptosis index decreased,caspase3,caspase9,bax decreased,bcl-2,c-myc increased.⑶Compared with IP+TMZ group: IP group and TMZ group arrhythmia scores increased,myocardial infarction area increased,SOD concentration decreased,CKMB concentration increased,MDA concentration increased,IL-6,TNF-α concentration increased,cell apoptosis The index increased,caspase3,caspase9,bax increased,bcl-2,c-myc decreased.The differences between the above groups are statistically significant(P>0.05)Conclusion:In this experiment,we can see that ischemia postconditioning treatment and trimetazidine preconditioning can alleviate myocardial ischemia-reperfusion injury.However,in the IP+TMZ group,no matter from arrhythmia score,myocardial infarction area,inflammatory factors,SOD,MDA,apoptosis protein expression and other indicators can be seen to be better than other groups,so we concluded that trimetazidine pretreatment plus ischemia ischemia postconditioning treatment has the protect effect of reducing myocardial ischemia-reperfusion injury.The injury is more alleviated than trimetazidine preconditioning or ischemic post-conditioning single-factor intervention,which is of great clinical significance.